This proposal delineates the principal investigator's plan for development of a career in academic Hematology. The candidate has demonstrated a commitment to research and a long-standing interst in blood-rated diseases, and is completing an academic fellowship in Hematology/Oncology. The University of Pennsylvania and, specifically, the mentorship of Dr. Craig Thompson, Scientific Director of the Abramson Family Cancer Research Institute, provides a stimulating and supportive environment for creative thought and rigorous scientific development. In multicellular organisms, extracellular signals are required to maintain survival in normal tissues. One way which these signals prevent programmed cell death in lymphocytes is through the promotion of nutrient uptake and cellular metabolism. Interference with these processes results in programmed cell death. Further-more, malignant tissues utilize glucose abnormally, and we hypothesize that this results from bypass of growth factor signals allowing unregulated glucose uptake and metabolism. The proposed experiments will address both the mechanism of extracellular signalmediated regulation of glucose metabolism in normal lymphocytes and its disruption in lymphoma. The specific aims include: 1) Study of the regulation of glucose uptake and metabolism in normal human lymphocytes, 2) Determination of the role of Akt in glucose metabolism and its cooperation with Myc and Bc1-XL in transformation in transgenic mice, and 3) Evaluation A the mechanism of increased glycolysis in lymphoma. With the input and participation of an advisory committee including Dr. Abass Alavi, Chief of Nuclear Medicine and Dr. Stephen J. Schuster, assistant professor of Hematology and Director of the Lymphoma Program at the University of Pennsylvania Cancer Center, this program provides a clear plan for the development of the candidate's projected academic career.